18-346822-G-T

Variant names:

• chr18-346822-G-T
• rs962198288
• NM_130386.3:c.800C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130386.3(COLEC12):​c.800C>A​(p.Thr267Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T267M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COLEC12 NM_130386.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

Genes affected

COLEC12 (HGNC:16016): (collectin subfamily member 12) This gene encodes a member of the C-lectin family, proteins that possess collagen-like sequences and carbohydrate recognition domains. This protein is a scavenger receptor that displays several functions associated with host defense. It can bind to carbohydrate antigens on microorganisms, facilitating their recognition and removal. It also mediates the recognition, internalization, and degradation of oxidatively modified low density lipoprotein by vascular endothelial cells. [provided by RefSeq, May 2018]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19165257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLEC12	NM_130386.3	c.800C>A	p.Thr267Lys	missense_variant	Exon 5 of 10	ENST00000400256.5	NP_569057.2
COLEC12	XM_011525741.3	c.749C>A	p.Thr250Lys	missense_variant	Exon 4 of 9		XP_011524043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLEC12	ENST00000400256.5	c.800C>A	p.Thr267Lys	missense_variant	Exon 5 of 10	1	NM_130386.3	ENSP00000383115.3
COLEC12	ENST00000582147.1	n.1008C>A		non_coding_transcript_exon_variant	Exon 5 of 9	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.094
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.014	D
Polyphen		0.39	B
Vest4		0.42
MutPred		0.33		Gain of MoRF binding (P = 0.0296);
MVP		0.30
MPC		0.45
ClinPred		0.30	T
GERP RS		2.4
Varity_R		0.083
gMVP		0.36
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs962198288; hg19: chr18-346822;